(BT05415) MOLECULAR MODELING & DRUG DESIGN

Unit I: Introduction to Molecular Modelling
Introduction to Molecular Modelling. What are models used for? Areas of application – Single
molecule calculation, assemblies of molecules. Reaction of the molecules. Drawbacks of
mechanical models as compared to graphical models. Co-ordinate systems two – matrix,
potential energy surface.
Unit III – Quantum Mechanics
Postulates of quantum mechanics, electronic structure calculations, ab initio, semi-empirical
and density functional theory calculations, molecular size versus accuracy. Approximate
molecular orbital theories.
Unit III: Empirical Force Field Models
Molecular Mechanisms, energy calculations, Bond stretch, angle bending, torsional term.
Electrostatic interaction- Van der waals interactions. Miscellaneous interaction.
Unit IV – Molecular Dynamics
Introduction, Molecular Dynamics using simple models. Dynamics with continuous potentials.
Constant temperature and constant dynamics. Conformation searching, Systematic search.
Applications to protein folding
Unit V – Comparative protein modeling
Modelling by Homology-the alignment, construction of frame work ,selecting variable regions,
side chain placement and refinement, validation of protein models –Ramchandran plot,
threading and ab initio modeling.
UNIT VI: Analog Based Drug Design
Introduction to QSAR. lead module, linear and nonlinear modeled equations, biological
activities, physicochemical parameter and molecular descriptors, molecular modelling in
drug discovery.
UNIT VII: Structure Based Drug Design
3D pharmacophores ,molecular docking, De novo Ligand design, Free energies and solvation,
electrostatic and non-electrostatic contribution to free energies.
UNIT VIII: Further applications on the design of new molecules
3D data base searching and virtual screening, Sources of data, molecular similarity and
similarity searching, combinatorial libraries – generation and utility,
TEXTBOOKS
1. Principles and applications of modelling by Leach
2. Molecular Modelling by Hans Pieter,Heltje & Gerd Folkens, VCH.
REFERENCES:
1. Chemical Applications of Molecular Modelling by Jonathan Goodman.
2. Computational Chemistry by Guy H, Grant & W. Graham Richards, Oxford University
Press.